This application addresses broad Challenge Area (05) Comparative Effectiveness Research and specific Challenge Topic, 05-CA-104*: Comparative Effectiveness Research on Cancer Treatment. We propose to address two distinct but related challenges: (1) development of a research agenda for cancer comparative effectiveness research (CCER) that takes into account both the feasibility of the research and its potential importance to relevant stakeholders;and (2) completion of several high priority and high quality assessments of the comparative effectiveness of alternative cancer treatments for specific clinical subsets of cancer patients. We will use a unique data resource that we have assembled over the past 12 years that is ideally suited to CCER and that makes it feasible to complete this ambitious scope of work within the grant period. The National Comprehensive Cancer Network (NCCN), an affiliation of 21 of the leading cancer centers in the United States, has been collecting detailed baseline, treatment, and outcome data on patients treated in member institutions since 1997. Using data from the NCCN Breast Cancer, Lung Cancer, Colorectal Cancer, and Non-Hodgkin's Lymphoma Outcomes Databases we propose to: Aim 1. Develop a set of candidate targets for cancer comparativeness effectiveness research by identifying specific treatment decisions for which there is an incomplete or non-existent evidence base and observed practice variation unrelated to patient characteristics. Aim 2. Prioritize these treatment decisions for CCER based on input from key stakeholders including the National Cancer Institute, the Centers for Medicare and Medicaid Services, state Medicaid plans, major private payers, patient advocates, and the oncology practice community. Aim 3. Conduct assessments of process-outcome linkage for 4 treatment decisions identified as high priority topics for CCER using data from the NCCN Outcomes Databases. This project will provide policy-makers and the research community with an empirically-based and systematic prioritization of research topics, thus increasing both the efficiency and the public health impact of the comparative effectiveness research enterprise. And by selecting 4 high priority topics for analysis using the clinically detailed data available in the NCCN Outcomes database, we anticipate that our findings can help to define and lead to more effective treatment for thousands or even millions of cancer patients in the near term. -- Relevance The four diseases we're proposing to study represent 48% of all cancer diagnoses in the United States. We are proposing to take a systematic approach to identifying aspects of care for these patients that may be suboptimal, and then conducting research that will identify how the effectiveness of their treatment could be improved.